Palladium-, ligand-, and solvent-free synthesis of ynones by the coupling of acyl chlorides and terminal alkynes in the presence of a reusable copper nanoparticle catalyst

Article abstract of DOI:10.1039/c3gc40980e

Supported copper nanoparticles are utilized for the first time as a highly efficient and reusable catalyst in the coupling of acyl chlorides and terminal alkynes to prepare various ynones. The reaction is carried out under palladium-, ligand-, and solvent

Full text of DOI:10.1039/c3gc40980e

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DOI: 10.1039/C3GC40980E
The coupling of acyl chlorides and
terminal alkynes was catalyzed by copper
nanoparticles under a palladium-, ligand-,
and solvent-free condition.

Green Chemistry
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Palladium-, ligand-, and solvent-free synthesis of ynones by the coupling
of acyl chlorides and terminal alkynes in the presence of a reusable
copper nanoparticle catalyst
Weijiang Sun,# Yan Wang,# Xuan Wu, and Xiaoquan Yao*
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
independently as catalyst in the reaction at room
temperature.20
palladium-free catalytic reaction was
Supported copper nanoparticles are utilized for the first time
as a highly efficient and reusable catalyst in the coupling
reaction of acyl chlorides and terminal alkynes to prepare
A
50 reported by Chowdhury and Kundu with CuI as catalyst, but
only moderate yields were observed and suffered higher
catalyst loading and much longer reaction time.21 Gallagher
and Maleczka developed a catalytic system consisting of CuCl,
CsF and polymethylhydrosiloxane.22 The reaction resulted in
55 moderate yields involving a in situ generation of a siloxyl
intermediate.
10 various ynones. The reaction is carried out under
a
palladium-, ligand-, and solvent-free condition. The catalyst
can be simply recovered and reused for several times without
significant loss in catalytic activities.
α,β-Acetylenic carbonyl derivatives (ynones) are of great
15 interest due to their extensive application in natural products
and organic synthesis. They are extremely versatile
intermediates for the preparation of heterocyclic derivatives.1
Many synthetic strategies for ynones have been reported.
Among them, the cross-coupling reaction of carboxylic acid
20 derivatives and stoichiometric metal acetylides was one of
important approaches to synthesize ynones, in which the
usage of magnesium2, silver3, cadmium4, silicon5, copper6,
tin7, lithium8, aluminum9, thallium10, gallium11, stibium12,
indium13, zinc14 and boron15 reagents and carboxylic acid
25 derivatives all led to the formation of ynones. However,
using a large amount of sensitive metal acetylides made the
reaction drastic and uneconomical. As a result, an alternative
catalytic coupling of acyl chlorides and terminal alkynes
utilizing palladium-copper catalyst, known as a Sonogashir-
30 type reaction, drew more attention.16 In the past few decades,
much progress has been made to improve this methodology,
and various palladium species were reported.17 Cox and his
co-workers utilized Pd(PPh3)2Cl2/CuI to proceed the reaction
at room temperature and shortened the reaction time
35 significantly.18 Nájera and co-workers reported an oxime
derived palladacycle as catalyst alone instead of Pd/Cu.19 The
reaction proceeded under a phosphine and copper free
condition at high temperature. Pd(OAc)2 were also ultilzed
In view of green and sustainable chemistry, many
recyclable catalytic system were reported for the coupling
reaction in recent years. Chen and Li reported the first
60 example in water by using Pd(PPh3)2Cl2/CuI as catalyst with
sodium lauryl sulfate as surfactant.23 Heterogenous palladium
also proved to be efficient catalysts in the coupling reaction,
24-27
in which sillica-immobilized palladium(II) catalyst could
also be used in water medium.28 On the other hand, supported
65 zinc bromide was also reported as an efficient recyclable
catalyst in the reaction.29
In recent years, there has been a great interest in using
nanoparticles as catalysts in organic reactions.30 Because of
easy preparation and being relative stable in air, the
70 nanoparticles of coinage metals were widely reported, and
there are many excellent examples on their applications as
catalysts.31 Based on our continuous investigation on copper
and silver nanoparticles catalyzed reactions,32 we wish to
report herein a palladium-, ligand- and solvent-free, copper
75 nanoparticles (Cu-nps) catalyzed cross-coupling reaction of
acyl chlorides and terminal alkynes for the synthesis of
ynones. The reaction proceeded smoothly under a mild
condition in the absence of ligands and solvents. A variety of
acyl chlorides and terminal alkynes were examined, and good
80 to excellent yields were achived with only 1 mol% of catalyst
loading. By using solid supporters, the catalysts can be easily
separated from the reaction mixture and reused for several
cycles without significant decrease in catalytic activities.
The copper nanocatalysts were prepared following the
85 reported procedure by using cupric acetate as raw material,
water as solvent, polyvinylpyrrolidone (PVP) as protecting
agent and sodium borohydride as reducing agent.33-34
Considering their convenience in handling and storage,
espically in catalyst recovery and product separation, two
40 Department of Applied Chemistry, School of Material Science and
Engineering, Nanjing University of Aeronautics and Astronautics,
Nanjing 210016, PR China. Fax: 86 25 52112626; Tel: 86 25 52112626;
E-mail: yaoxq@nuaa.edu.cn
# These authors contributed equally to this work.
45 † Electronic Supplementary Information (ESI) available: Experimental
procedures, spectroscopic and analytical data. See DOI: 10.1039/
b000000x/
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kinds of supported catalysts, γ-Al2O3- and sillica gel-
the promotion of any ligand (entry 1, Table 1), whereas other
supported copper nanoparticles were also synthesized 20 organic solvents, such as DCM, MeCN and DMF, resulted in
respectively, and their TEM images were shown in Fig. 1.
low conversions (entries 2-4). SuperisinglDy,OwI: 1h0e.n10tV3hi9ee/wcCAa3rtGtaiCclly4e0tOi9cn8li0nEe
reaction was carried out under a solvent-free & ligand-free
condition, Cu-nps catalyst showed the highest activity and up
to 98% of yield was achieved (entry 5).
25
Other bases, such as K2CO3, N,N-diisopropylethylamine,
trioctylamine and 2,6-lutidine, were also evaluated for the
reaction instead of TEA under neat condition. However, all
of them lead to very poor results (entries 6-10). Reducing the
amount of Et3N led to the decrease in reactivities
30 significently (entries 11-12), and the reaction did not work at
all in the absence of TEA as base (entry 13). The same tend
was also obsevrved when reducing the ammount of Cu-nps
catalyst (entry 14). On the other hand, Ag-nps was also
scaned as catalyst instead of copper, but no reaction
35 occurred(entry 15).
5
Fig. 1 The TEM image of supported copper nanoparticles:
Cu-nps/silica gel (left); Cu-nps/γ-Al2O3 (right)
The nature of the supporting materials proved to be an
important influential factor to catalytic activities of
nanoparticles in our previous report.32c To further
improvement of the reaction, espically the convenience in
40 recovering and recycling the catalyst, γ-Al2O3- and sillica
gel- supported copper nanoparticles were employed as
catalysts. It is worthy to note that the supported Cu-nps could
decrease the catalyst loading significiently. Sillica gel-
supported catalyst gave the best result, and even 1 mol% of
45 catalyst is enough to generate an 95% yield of the desired
product (entries 17-20).
It can be seen from the images that the two catalysts have
similar particle size, but sillica gel supported Cu-nps exhibit a
10 smaller size, better morphology and more uniform distribution.
With the prepared Cu-nps catalysts, we then examined them
in the reaction of acyl chlorides and terminal alkynes toward
ynones. The cross-coupling reaction of benzoyl chloride and
phenylacetylene was selected as the prototype, and the results
15 were summirized in Table 1.
Cu-nps was ultilized alone to catalyze the reaction at first
with toluene as solvent and Et3N as base. After overnight
reaction at 40oC, 82% of desired product was isolated without
Table 1 Copper nanoparticles catalyzed cross-coupling reaction of benzoyl chloride and phenylacetylene a
catalyst (mol %)
solvent
base (equiv)
yield (%)b
entry
1
2
3
4
5
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
toluene
DCM
MeCN
DMF
free
TEA (3)
TEA (3)
TEA (3)
TEA (3)
TEA (3)
82
12
49
N.D.
98
6
7
8
9
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
Cu-nps (5)
free
free
free
free
free
free
free
free
free
free
free
free
free
free
free
K2CO3 (3)
2,6-lutidine (3)
i-Pr2NEt (3)
(n-C8H17)3N (3)
PhNMe2 (3)
TEA (2)
N.D.
N.D.
32
N.D.
N.D.
87
64
N.D.
87
N.D.
N.D.
98
89
98
10
11
12
13
14
15
16
17
18
19
20
TEA (1)
free
TEA (3)
TEA (3)
TEA (3)
TEA (3)
TEA (3)
TEA (3)
Cu-nps (2.5)
Ag-nps (5)
free
Cu-nps/γ-Al2O3 (5)
Cu-nps/γ-Al2O3 (1)
Cu-nps/silica gel (5)
Cu-nps/silica gel (1)
TEA (3)
95
a Reaction conditions: phenylacetylene (0.5 mmol), benzoyl chloride (1.5 equiv), solvent (2 mL), 40 °C overnight. b The yields were determined by GC
50 with dimethyl phthalate as internal standard.
2
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Table 2 Synthesis of ynones by coupling of acyl chlorides with terminal alkynes.a
yield
yield
entry acyl chlorides
alkynes
products
entry acyl chlorides
alkynes
products
(%)b
(%)b
O
O
O
O
Cl
Cl
1
92
12
13
14
89
MeO
MeO
MeO
1a
2a
2b
3a
1c
2c
OMe 3l
O
O
O
O
O
O
Cl
Cl
Cl
Cl
2
98
91
96
94
90
89
Cl
Cl
1a
3b
1d
2a
2b
3m
O
O
O
3
Cl
Cl
OMe
Cl
MeO
1a
2c
3c
3d
3e
1d
1d
3n
3o
O
O
O
4
15
Cl
Cl
Cl
Cl
Cl
OMe
MeO
1a
2d
2e
2c
O
O
O
O
Cl
5
80
79
88
16
17
18
87
82
81
Cl
OMe
Br
Br
OMe
1a
1e
1e
2a
2b
3p
O
O
O
O
Cl
Cl
6
OMe
C4H9
C4H9
OMe
1a
2f
3f
O
3q
3r
O
O
O
Cl
OMe
7
Cl
OMe
O
MeO
OMe
1b
2a
2d
3g
1e
2c
O
O
8
82
78
81
80
19
20
21
22
84
84
71
35
Cl
Cl
Cl
Cl
1b
3h
1f
2a
2a
2a
3s
3t
O
O
O
O
Cl
9
Cl
C4H9
C4H9
1b
2f
3i
1g
1h
O
O
Cl
10
11
MeO
MeO
1c
2a
3j
O
3u
O
Cl
MeO
MeO
MeO
1c
2b
3k
1h
2c
3v
a Reaction conditions: alkyne (0.5 mmol), acyl chloride (1.5 equiv), Et3N (3 equiv), supported Cu-nps (1 mol %), 40 °C overnight. b Isolated yield.
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Subsequently, the scope of the reaction was investigated
were employed as substrates to synthesis ynones under a mild
with various acyl chlorides and terminal alkynes under the 45 condition, and good to excellent yields were acheived. Further
optimized condition (entry 20, Table 1), and good to excellent
yields were achieved (Table 2). It can be seen from Table 2
that most of aromatic alkynes with electron-donating or
electron-withdrawing substitutents resulted in excellent yields,
more, the catalysts could be easily separated and reused for
several cycles without significant decrease in catalytic activity.
The detailed mechanism, the effect of particle size35 and
particle support as well as the scope of the reaction are
5
except the brom-substituted alkyne 2e (entries 1-4 vs entry 5, 50 currently under further investigations.
Table 2). It is worthynote that aliphatic alkyne 2f, which was
This work was financially supported by the National
less active substrate in many previous reports, also gave 79%
Natural Science Foundation of China (21172107) .
10 of yield to the desired product (entry 6). On the other hand,
aromatic acyl chlorides were suitable substrates. Even with
the aromtic acyl chlorides 1e and 1f as substrates, which had
steric hindrance at the ortho position, 81-87% yields were
achieved sucessfully (entries 16-19). Aliphatic acyl chlorides
15 also gave good to moderate results with 2a as terminal alkyne
(entries 20-21). However, a lower yield was observed in the
reaction of 1h and 2c (entry 22).
Notes and references
1
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55
60
65


Cu-nps/silica gel
Cl
3 equiv. TEA, neat
1a
10 mmol
3a
86% yield
2a
15 mmol
Scheme 1. Gram-scale reaction of 1a and 3a.
2
3
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out, and 86% of isolated yield was achieved.
70 4
Table 3 Recycling studiesa.
5
6
7
first run
second run
third run
entry
supporter
yield (%)b
yield (%)b
yield (%)b
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1
2
γ-Al2O3
silica gel
silica gel
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95
92
83
90
88
78
84
85
3c
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a Reaction conditions: alkyne (0.5 mmol), acyl chloride (1.5 equiv), Et3N
(3 equiv), 40 °C overnight, supported Cu-nps (1 mol %). b Yield
25 determined by GC using dimethyl phthalate as internal standard. c
Reaction in 2 mmol scale.
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One of the advantages of heterogeneous catalysts is their
easy separation from the reaction mixture. The supported Cu-
nps catalyst could be separated and recovered conveniently by
30 centrifugation from the reaction mixture, and then, new
substrate and base were added to set up a new reaction.
Following this procedure, the catalyst was recycled effectively,
and the results were summarized in Table 3. Obviously, the
silica gel-supported catalyst showed much better recycling
35 ability than the Al2O3-supported (entries 2-3 vs. entry 1, Table
3). On the other hand, in order to further investigate the
reusability of the catalyst, the scale of the reaction was
increased from 0.5 mmol to 2 mmol, and there was no obvious
decrease in catalytic activities observed after several recycles.
85
95
1615.
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40
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3334.
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35 As a primary result for the effect of particle size, we prepared the
copper NPs without surfactant, and the size of the particles was
around 50 μm with a wide distribution. Only 76% of 3a was
obtained with 5 mol % catalyst.
30
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